Home > Publications database > Untersuchungen zur Funktion von Ca$^{2+}$-aktivierten CI Kanälen und cAMP-gesteuerten Kationenkanälen bei der Erzeugung des Rezeptorstroms in Riechzellen der Ratte |
Book/Report | FZJ-2020-00435 |
2000
Forschungszentrum Jülich GmbH Zentralbibliothek, Verlag
Jülich
Please use a persistent id in citations: http://hdl.handle.net/2128/23982
Report No.: Juel-3778
Abstract: cAMP-gated ion channels in olfactory sensory neurons are composed of three distinctsubunits, denominated CNC$\alpha$3, CNC$\alpha$4 and CNC$\beta$1b. The channels are cooperativelyactivated by cAMP, and the cAMP-sensitivity is modulated by ca modulin in a Ca$^{2+}$-dependent matter. cAMP-sensitivity, modulation by calmodulin, gating behavior and-ionic selectivity of the channels are determined by the quarternary structure. In this study, the kinetics of the modulation of the cAMP-sensitivity of these channels bycalmodulin were determined by performing patch-damp recordings in the inside-outconfiguration, revealing a bi-phasic time-course of the modulation. By comparing thekinetics of different heterologously coexpressed channels and of native channels fromrat olfactory sensory neurons, the function of the modulatory subunits CNC$\alpha$4 andCNC$\beta$1b could be determined. This comparison yielded the highest congruency betweenthe properties of CNC($\alpha$3$\alpha$4$\beta$1b) channels and of the native channel, stronglysuggesting that the native channel must contain all three different subunits, in orderto properly perform its physiological function in the olfactory transduction cascade. Themolecular mechanism, by which Calmodulin modulates the ligand-sensitivity of CNG-channels,has yet to be determined.CNG-channels conduct Na$^{+}$, K$^{+}$ and Ca$^{2+}$-Ions. Under physiological conditions, thechannels primarily conduct Ca$^{2t}$-ions, thus serving as functional Ca$^{2+}$-channels in theolfactory transduction cascade. Ca$^{2+}$-ions entering the cell through CNG-channelsactivate Ca$^{2+}$-activated Cl channels, which conduct a substantial fraction of the receptorcurrent. In this study, activation of these channels by Ca$^{2+}$ and time-dependentinactivation were observed in dissociated olfactory receptor neurons from rats usingelectrophysiological recordings. Furthermore, the concentrations of chloride inside thecellular lumen and the olfactory mucus were determined using analytical electronmicroscopical measurements in order to determine the electrochemical potentialrelevant for the polarity of the chloride current $\textit{in vivo}$. These measurements validate thenotion that chloride ions carry an excitatory current in the olfactory transduction cascadeto further amplify the primary cationic current carried by CNG-channels.
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